N-Acetylcysteine Mitigates Histopathological and Ultrastructural Alterations Induced by Chronic Usage of Acetaminophen in the Rat Renal Cortex

Abstract

Background: Acetaminophen or N-acetyl-p-aminophenol (APAP) is a potent analgesic and antipyretic drug that is widely used. N-Acetylcysteine (NAC) is a synthetic antioxidant, acting as a free radical scavenger.Aim of the work: This work was designed to demonstrate the effect of NAC on the histological changes induced by chronic usage of acetaminophen in the renal cortex.Materials and methods: Forty male albino rats distributed into four groups were utilized. Control group: given distilled water. NAC-group: given NAC (150 mg/kg/day), orally, once daily for 4 weeks. Aceta-group: given Acetaminophen (APAP 300 mg/kg/day) orally, once daily for 4 weeks. Aceta+NAC group: given Acetaminophen (APAP 300 mg/kg/day) orally then NAC (150 mg/kg) orally 2 hours after oral APAP, once daily for 4 weeks. Small specimens of the renal cortex were obtained and processed for light and electron microscopic studies. Blood urea nitrogen (BUN) and serum creatinine levels were assessed. Morphometric and statistical studies were also performed.Results: Chronic usage of acetaminophen resulted in distortion and shrinkage of some glomeruli and partial destruction of Bowman's capsule. Proximal convoluted tubules showed dilatations, degenerative changes and loss of the apical brush border. Mononuclear cellular infiltration and deposition of collagenous fibers in the renal interstitium were also demonstrated. By electron microscope, glomerular basement membrane showed irregular thickening and loss of its trilaminar appearance. Cells lining the proximal convoluted tubules showed dense irregular nucleus, cytolplasmic vacuoles and loss of apical microvilli. These changes were accompanied by significant elevations in the serum levels of BUN and creatinine. NAC administration provoked partial improvement in the renal histology and a significant decline in serum levels of BUN and creatinine.Conclusion: N-acetylcysteine could attenuate histological and biochemical changes induced by chronic usage of acetaminophen in the rat renal cortex.